Journal article
Virus-specific antibody, in the absence of T cells, mediates demyelination in mice infected with a neurotropic coronavirus
The American Journal of Pathology, Vol.166(3), pp.801-809
03/2005
DOI: 10.1016/S0002-9440(10)62301-2
PMCID: PMC1602352
PMID: 15743792
Abstract
Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1 −/− mice lacking normal expression of activating Fc receptors (FcRγ −/− ) and by ∼76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.
Details
- Title: Subtitle
- Virus-specific antibody, in the absence of T cells, mediates demyelination in mice infected with a neurotropic coronavirus
- Creators
- Taeg S Kim - University of Iowa, Iowa City, IowaStanley Perlman - University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- The American Journal of Pathology, Vol.166(3), pp.801-809
- DOI
- 10.1016/S0002-9440(10)62301-2
- PMID
- 15743792
- PMCID
- PMC1602352
- NLM abbreviation
- Am J Pathol
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Publisher
- American Society for Investigative Pathology; United States
- Grant note
- R01 NS 40438 / NINDS NIH HHS R01 NS040438 / NINDS NIH HHS
- Language
- English
- Date published
- 03/2005
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777469002771
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